99mTc-containing estrogen like molecules for in vivo molecular imaging estrogen receptor (ER) positive tumors is proposed. Conventional tumor targeted imaging methods include 99mTc-chleated tumor binding macromolecular carriers such as tumor specific antibody or peptides. However, the macromolecular carriers are often insensitive in imaging solid tumors due to poor permeability. Furthermore, their slow clearance rate from the body results in low image quality due to high uptake in and poor clearance from non-target sites. On the other hand, imaging agents involving small molecule carriers are considered as a suitable alternative to overcome the limitations of macromolecular carriers. Earlier studies used radiohalogenated estradiol as small molecule carrier for imaging ER+ tumors. However, in vivo deiodination has been a persistent problem with radioiodinated estradiol. Imaging agents based on 99mTc is the most desirable due to its ideal imaging properties, wide availability, and low cost compared to all other radionuclides. A few estrogen based 99mTc-containing molecules with ER specificity have been reported by attaching 99mTc complexes at suitable positions. However, development of these molecules was focused primarily on ER binding characteristics without much emphasis on SHBG binding properties. Consequently, even the molecules with good ER affinity ex vivo, performed poorly in biodistribution studies. The in vivo target tissue uptake of estrogen like steroidal molecules is intimately related to the binding of the steroids to sex hormone binding globulin (SHBG). SHBG protects the sex steroids from metabolism and mediates the uptake of estrogens in target tissues by SHBG receptors on the cell surface. Therefore, the design of any steroid radiopharmaceutical must not only take into account the ER affinity, but also SHBG binding capability. The estrogen based small molecules presented in this proposal is based on integrating 99mTc metal ion into the steroidal skeleton by isosteric substitution of a carbon atom in the steroid. This approach gives new classes of estrogen mimics 1-2 that are similar in size, and shape to the native estrogen, and, thus, are termed as 'estrogen mimics. Molecular modeling indicates that estrogen mimics resemble native estrogen in both ER and SHBG binding characteristics. The estrogen mimics 1-2 will be useful in radioimaging of ER+ breast cancers. [unreadable] [unreadable] [unreadable]